Rearrangements, Claisen rate enhancement

The aqueous rate-enhanced Claisen rearrangement of glycoorganic compounds was shown to proceed in excellent yields [57]. The water solubility of the reactants was induced by grafting a free sugar onto the allyl vinyl ether moiety moreover, the sugar functioned as a chiral template and gave highly crystalline diastereomers which were easily separable to yield pure enantiomers after enzymic hydrolysis. This method allows the preparation of either enantiomerically pure (R)- or (S)-l,3-diol (Scheme 1). 

The fact that the two terminal fluorines do enhance the rate of Claisen rearrangement is demonstrated by the Johnson-Claisen rearrangement of tnonofluoroallylic alcohol 3, which gives only a 41 % yield of /f-fluoro ester 4 after 48 hours at 140 C.2y... 

Microwave irradiation strongly enhances the rate of Claisen rearrangement. This helps in solving the problem of the long-term heating under conventional conditions. The yield of rearranged produets in classical method is about 85% in 6 h where as it was inereased to 92% in 6 min by using N,N-dimethylformamide as solvent under mierowave irradiation. 

Chorismate Mutase catalyzed Claisen Rearrangement- 10 rate enhancement over non-enzymatic reaction... 

Classical organic reactions that have been carried out in water include, among others, the Diels-Alder reaction, the Claisen rearrangement, aldol condensations, Michael additions, and nucleophilic substitutions. In the Diels-Alder reaction, for example, water has been found to increase the reaction rate and to enhance the endoselectivity 120). Two reviews summarize the results for organic reactions in water 121). 

Acceleration of Claisen rearrangements.2 The Claisen rearrangement of an allyl vinyl ether is markedly accelerated by a stabilized a-sulfonyl carbanion at the 2-position. Thus 1 and 2 rearrange to the y,d-unsaturated ketone 3 in the presence of potassium hydride and 18-crown-6 at moderate temperatures. Rates can be further enhanced by addition of HMPT. Substitution of methyl groups on either the allyl or vinyl units does not affect the regioselectivity but can accelerate the rate of rearrangement. 

For the ort/io-Claisen rearrangement of allyl p-io y ether shown in Eq. (5-50), the rate enhancement with increasing solvent polarity is modest, in agreement with a cyclic process involving concerted bond-making and -breaking on activation [153]. 

A C(6) donor substituent exerts a similar enhancing efiect on the rate of the Claisen rearrangement, though somehow less pronounced than the rate-accelerating effect of the 2-silyloxy substituent (approx. 1.4 kcal mol" ). As Curran and coworkers reported, " this vinylogous anomeric effect of the C(6) donor substituent is especially effective in glycal systems. The energy of the TS is decreased by assist-... 

The rate enhancement observed with polar solvents corresponds well with a dipolar transition state in the Claisen rearrangement see Section 7.2.2.12. 

Although cycloadditions and rearrangements often proceed without catalysts, the selectivity of the reaction and the reactivity of very reluctant molecules can be enhanced by a Lewis acid. The Diels-Alder reaction can be performed at enhanced reaction rate in ionic liquids with the addition of ZnCl2 (eq. (4)) [42]. The Claisen rearrangement was also reported to be superior if catalyzed by Sc(OTf)3 in ionic liquids [43]. 

Rate enhancements of Claisen rearrangements can be achieved by the formation of anions a to C-2 (which can formally be considered as strong n-donors in position 2). Ester enolatcs of lithium87 88 91. sodium92-95, magnesium96-98 and zinc" have been widely used to effect chargc-accelerated rearrangements. 

The catalytic influence of ammonium chloride on the rate of the reaction was discussed by Claisen in his first report19. Since then, numerous catalysts have been introduced to affect rate enhancements of Claisen rearrangements, e.g., Bronsted and Lewis acids, bases or transition metal complexes. The literature concerning catalytic effects in the Claisen rearrangement has been thoroughly covered until 1984 0,122. 

It is possible to enhance the rate of a Claisen rearrangement, especially in the enolate Claisen reaction. Denmark et al. showed that other carbanionic centers accelerate the Claisen rearrangement (as in Table 11.23).467 Generation of the anion of sulfone 631 (sec. 8.6.A) with various bases led to acceleration of the reaction relative to the thermal reaction of 631 and also influenced the syn/anti ratio (632/633). In general, a donor group at the allyl position accelerates the rate and the presence of an amino stabilizing group increases the rate even more. 

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